Photochromism refers to the phenomenon that the color of either compounds, which change color when exposed to UV or visible light, or products containing such compounds, show a reversible color change by light. Photochromic compounds exist in at least two isomeric forms having different physical properties such as absorption properties and refractivity and can be transformed from one form to another form by light excitations at prescribed wavelengths.
Photochromic materials which can show a reversible color change by light are applicable in various fields, including photorecorders, photoswitches and modulators. For example, diarylethene compounds change color when exposed to UV light, and then return to their original color when irradiated with light of a different wavelength. Since such compounds were synthesized for the first time in the year 1985, they have been known to be stable photochromic compounds which do not exhibit any heat-induced color change after being exposed to light. In addition, various types of derivatives have been synthesized, and among them, diarylethene compounds substituted with fluorine are known to show high stability and very fast photochromism (Takeshita, M. et al., Chem. Commun., 1807, 1996; Irie, M., Chem. Rev., 1685, 1996).
Meanwhile, diarylethene compounds are soluble in most organic solvents, but are poorly soluble in water. For this reason, the application thereof in the biological field which is based on the aqueous solution phase is extremely limited. Recently, there was a report that diarylethene compounds can be converted to water-soluble compounds by introducing ethylene glycol thereinto (Hirose, T. et al., J. Org. Chem., 7499, 2006). In addition, Japanese Patent Publication No. 2003-246776 discloses a method of crosslinking biomolecules having a photochromic molecule and a thiol group with a maleimide group in order to provide cross-linkable photochromic molecules, which are obtained by reversibly changing the structure of biofunctional molecules, and to provide biofunctional molecule derivatives capable of producing mechanical energy. However, such molecules are difficult to apply in the biological field, because they are not water-soluble photochromic molecules.
Accordingly, there is an urgent need to develop biomolecule detection technology which can easily detect signals not only with an UV-VIS spectrophotometer but also visually using photochromic compounds showing a reversible color change by light of specific wavelengths, and which can reduce undesired background signals to greatly improve detection sensitivity.
The present inventors have prepared water-soluble photochromic compounds by linking a functional group rendering photochromic molecules water-soluble to a functional group capable of covalently bonding to biomolecules and have found that, when the prepared water-soluble photochromic compounds are labeled to biomolecules, such as proteins, nucleic acids or the like, the photochromic compounds labeled to the biomolecules generate color change-inducing signals by light of specific wavelengths, such that signals can be detected even visually without using a separate device, and the detection sensitivity of biomolecules to be measured can be greatly improved, thereby completing the present invention.